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CaptionDETECTIVE WORK: Vamsi Mootha and colleagues discovered the elusive protein driving mitochondria. “Thanks to the Human Genome Project, freely downloadable genomic databases, and a few tricks,” he says, “we were able to get to the bottom of it.”

Mitochondria those battery–pack organelles that fuel the energy of nearly every living cell, have an insatiable appetite for calcium. The mitochondria of most organisms eagerly absorb this chemical compound. Because calcium levels link to many essential biological processes—not to mention conditions such as neurological disease and diabetes—scientists have been working for half a century to identify the molecular pathway that enables these processes.

After decades of failed effort that relied on classic biochemistry and membrane protein purification, Vamsi Mootha, an HMS professor of systems biology at Massachusetts General Hospital, and colleagues have discovered the linchpin protein that drives mitochondria’s calcium machinery. Their findings appeared online in Nature on June 19.

With their earlier discovery of MICU1, a protein essential for calcium uptake, as a point of reference, the researchers scoured a range of genomic databases for proteins whose activity profile mirrored that of MICU1. One protein with no known function stood out. The researchers named it mitochondrial calcium uniporter, or MCU.

“Scientists studying the nexus of energy metabolism and cellular signaling will be particularly interested in MICU1 and MCU,” says Mootha. “It’s still very early, but these proteins could prove to be valuable drug targets for diseases ranging from ischemic injury and neurodegeneration to diabetes.”